IF YOU could gaze into a crystal ball and discover whether your newborn baby might have health problems, would you want to know? This month, doctors in Boston will begin sequencing the genomes of healthy babies for the first time to explore the benefits and risks of sequencing at birth.

“We’ve been at an impasse for the last few years – we’ve had the technology to deliver information about future health, but we’ve not been able to use it because of all the issues around it,” says Robert Green of Harvard Medical School, who is conducting the BabySeq project alongside Alan Beggs at Boston Children’s Hospital.

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Pregnant women already have blood tests to assess their risk of passing on certain genetic diseases, such as cystic fibrosis. Those at high risk may choose to have further tests, such as amniocentesis, to determine if their unborn child has chromosomal abnormalities. But we’re on the cusp of knowing so much more.

In 2012, two groups showed that it is possible to sequence a fetus’s entire genome using fetal DNA circulating in the mother’s blood. While this is still some way from being used in the clinic, whole genome sequencing at birth is not. “Despite the well-recognised limitations in the predictive value of sequencing, there are many companies out there that feel they could be offering newborn sequencing right now,” says Green. “We felt it was our scientific responsibility to begin this kind of sequencing so if harms do occur we are available to mitigate them and have an understanding of them, before it is launched unmonitored on an unsuspecting public.”

“It’s our responsibility to work out what harms may occur before it is launched on an unsuspecting public”

Babyseq project

When babies are born, a spot of blood is routinely taken from their heel and analysed for signs of up to 30 treatable diseases. In the BabySeq project, 240 healthy babies born at the Brigham and Women’s hospital in Boston, and 240 babies in intensive care at Boston Children’s hospital will have their genome sequenced alongside the heel prick test, or have the heel prick test alone.

The team will carry out whole genome sequencing, looking at 1700 protein-coding genes that are strongly associated with diseases that begin in childhood. This could include Usher syndrome, which causes deafness and gradual vision loss. They will also be looking for mutations linked to diseases that occur in older children or adults that can be mitigated in childhood, such as familial adenomatous polyposis (FAP) in which polyps grow in the colon and eventually turn cancerous. And they will hunt for genes associated with incurable childhood conditions, such as Rett syndrome, where advance warning should mean parents are better prepared. At the moment, a healthy baby would not be screened for any of these conditions unless there was a family history of the disorder.

The results of the analysis will be summarised and explained to parents by a geneticist and a genetic counsellor. The summary will also be given to the infant’s paediatrician and used to guide their medical care. For example, it might mean a child with Usher syndrome is fitted with a cochlear implant earlier or a child with FAP has regular checks for colon polyps, says Caroline Weipert, one of BabySeq’s genetic counsellors. The team will monitor the child, parents and their physician for at least five years.

The team will not look for any gene mutations associated with adult diseases such as Alzheimer’s or breast cancer in their analysis.

Parents will not have access to their child’s raw data unless they request it – which they can do at the end of the project. “We are uncomfortable about releasing raw data as someone could analyse it inappropriately,” says Green. “But if the family insists, they can request it from the lab who may release it after a discussion with the parents.”

Genetic predictions

Might it be possible for a parent to later discover other traits about their child? “They won’t be able to discover much,” says Robert Plomin, professor of behavioural genetics at King’s College London. “People will be told by companies ‘yeah you can predict intelligence and musical ability and sport’, but you can’t.”

The genetic heritability of traits that we know most about are those for height and weight, he says. “That could come in useful for predicting which of your kids might be prone to obesity so you can keep an eye on their diet or lifestyle.”

Plomin says that the rise of genetic sequencing in children is inevitable: “That’s what’s good about this project – it’s going to happen sometime, so let’s see what the problems are now in a randomised trial.”

It’s important to study the impact of genomic screening in a safe and controlled manner, agrees Donna Dickenson, an emeritus professor of medical ethics at the University of London. “Market forces are driving personalised medicine to a considerable extent.” Dickenson also highlights some of the ethical implications: is the medical benefit to the child greater than the harm of removing the child’s right to choose? Might styles of parenting be affected?

“Is the medical benefit to the child greater than the harm of removing their right to choose?”

“We know the questions that the world has about this issue, and we have to start trying to answer them,” says Green, “but we’re not going to be able to do that by speculating. We answer them by starting a project in a carefully monitored environment, so that if something goes awry or causes unexpected distress, we are in a position to say ‘wait, stop, let’s not go down this road’, and then document the fact that it has happened.”